Outcome of multiple subpial transections for autistic epileptiform regression.

Treatment options for atypical forms of Landau-Kleffner syndrome (LKS) are not well delineated. Many patients with typical LKS fail to respond to antiepileptic drug treatment, but some benefit from multiple subpial transections (MSTs). The authors report seven patients with autism or autistic epileptiform regression who responded in varying degrees to MSTs after failed medical management. These patients derived from an original cohort of 36 children (29 males, seven females, ranging from 2 years, 3 months to 11 years, 3 months, mean age = 5 years, 8 months) with a history of language delay or regression, as well as varying degrees of social and behavioral abnormalities, who were evaluated with video-electroencephalogram (EEG) monitoring over a 2-year period. Fifteen patients had clinical seizures (11 of the 19 children with autistic epileptiform regression and four of 12 autistic children). Epilepsy was refractory to medication in seven. Surgical treatment variously involved MSTs of the left neocortex in temporal, parietal, and frontal regions, often including regions within the classic perisylvian language areas. One patient also had a left temporal lobectomy. In all seven patients, seizure control or EEG improved after MSTs. Language, social, and overall behavior improved to a moderate degree, although improvements were temporary in most. Autistic epileptiform regression resembles LKS in that both may respond to MST. MST is used to treat epilepsy in eloquent regions. The responsiveness of autistic epileptiform regression to MST buttresses the argument that autistic epileptiform regression is a form of focal epilepsy.     

Focal epileptiform spikes in conjuction with K-complexes.

Dyshormia or epileptiform spikes occurring within K-complexes have been described in patients with generalized epilepsy, with one study reporting that generalized spikes occurred frequently in association with K-complexes. We report the rate of focal epileptiform spikes occurring within K-complexes in localization-related epilepsy. Presurgical or diagnostic long-term video-EEG results of 40 consecutive patients with epilepsy (13 patients with right temporal lobe epilepsy, 20 patients with left temporal lobe epilepsy, and 7 patients with frontal lobe epilepsy) were reviewed. Sleep samples were reviewed and the numbers of K-complexes, spikes, and spikes within K-complexes were recorded. The comparison group consisted of 40 consecutive patients with nonepileptic events who were monitored with long-term video EEG. Focal epileptiform spikes occurring within K-complexes occurred in 2 of 13 (15%) patients with right temporal lobe patients, 6 of 20 (30%) patients with left temporal lobe, and 3 of 7 (42%) patients with extratemporal lobe epilepsy. In most patients, spikes occurring during K-complexes were rare. We identified spikes occurring during K-complexes in patients with localization-related epilepsy. The sharply contoured components of K-complexes or associated sleep spindles may obscure focal spikes within K-complexes. Nevertheless, K-complexes may be associated with focal epileptiform discharges.     

CSWS-related autistic regression versus autistic regression without CSWS

Continuous spike-waves during slow-wave sleep (CSWS) and Landau-Kleffner syndrome (LKS) are two clinical epileptic syndromes that are associated with the electroencephalography (EEG) pattern of electrical status epilepticus during slow wave sleep (ESES). Autistic regression occurs in approximately 30% of children with autism and is associated with an epileptiform EEG in approximately 20%. The behavioral phenotypes of CSWS, LKS, and autistic regression overlap. However, the differences in age of regression, degree and type of regression, and frequency of epilepsy and EEG abnormalities suggest that these are distinct phenotypes. CSWS with autistic regression is rare, as is autistic regression associated with ESES. The pathophysiology and as such the treatment implications for children with CSWS and autistic regression are distinct from those with autistic regression without CSWS.     

Autistic epileptiform regression

Autistic regression is a well known condition that occurs in one third of children with pervasive developmental disorders, who, after normal development in the first year of life, undergo a global regression during the second year that encompasses language, social skills and play. In a portion of these subjects, epileptiform abnormalities are present with or without seizures, resembling, in some respects, other epileptiform regressions of language and behaviour such as Landau-Kleffner syndrome. In these cases, for a more accurate definition of the clinical entity, the term autistic epileptifom regression has been suggested. As in other epileptic syndromes with regression, the relationships between EEG abnormalities, language and behaviour, in autism, are still unclear. We describe two cases of autistic epileptiform regression selected from a larger group of children with autistic spectrum disorders, with the aim of discussing the clinical features of the condition, the therapeutic approach and the outcome.     

A comparison between averaged spikes and individual visually-analyzed spikes in rolandic epileptiform discharges

PURPOSE:This study compared some morphological features of individual rolandic epileptiform discharges, used to obtain an averaged estimate, with those of the resulting estimate. METHOD: Twenty-four averaged discharges from EEGs of 24 children showing rolandic spikes were compared with 480 individual discharges used in the averaging. The analysis was based on the occurrence of tangential dipole and "double spike" patterns. RESULTS: In 15 averaged discharges the tangential dipole pattern was found. Individual spikes used in the averaging process displayed the same pattern in 35-100% of them; in the remaining 9 averaged discharges, up to 20% of the individual spikes showed the same pattern, although this was not found in the averaged waveforms. "Double spike" pattern was found in 11 of the averaged waveforms and was recognized in 50-100% of its individual discharges, whereas up to 45% of individual spikes showed this pattern without expression in the averaged waveform. CONCLUSION: When visually analyzing an EEG with rolandic spikes, caution should be exercised in characterizing these patterns, since a few discharges showing them may not be expressed in the averaged waveform and the clinical correlations proposed for these patterns may not apply.     

Levetiracetam-induced reversible autistic regression

Levetiracetam is a commonly prescribed antiepileptic drug, and is generally well tolerated, but can eventually cause behavioral disturbances. These disturbances seem more frequent in children and in patients with a previous psychiatric history. We report on reversible autistic regression induced by levetiracetam in a 6-year-old girl with spastic cerebral palsy, mild cognitive deficiency, and focal epilepsy. She was diagnosed with pervasive developmental disorder, and demonstrated mild to moderate impairment in pragmatic language and interactions with peers. After the introduction of levetiracetam, she developed stereotypies, and her social and communicative skills deteriorated severely. She also exhibited mood lability. When the medication was discontinued, a dramatic response occurred, with a complete resolution of new abnormal findings. Levetiracetam can provoke unusual behavioral adverse effects in certain patients who are biologically more vulnerable.     

Assessment of a computer program to detect epileptiform spikes

This study compares an automated spike detection program to a group of 6 electroencephaographers. Since group members varied in experience, an expertise factor was devised to weight their scoring. EEGers underscored epileptiform events on 6 records in a manner analogous to the computer's storage of EEG segments. A summation of expertise factors was determined for every event. This sum was normalized and interpreted as a probability the event would be called a spike by a given EEGer. The performance of each scorer and of the computer at different amplitude thresholds was analyzed based on this probability. Higher rated scorers identified more subtle events. Lowering the threshold of the computer program produced a comparable increase in sensitivity. The increase in total events detected by the computer was linear over the range studied. While the proportion of false positive detection increased with lowering threshold, our readers have not found a moderate number of these distracting. We conclude that the computer system, while not as specific as an EEGer, can be as sensitive and can be a reliable screening editor for large amounts of monitoring data. On balance it is more effective than an EEGer for this limited purpose.     

Autism and visual agnosia in a child with right occipital lobectomy

OBJECTIVES—Autistic disorder is a developmentalhandicap with an unknown neurological basis. Current neuropsychologicalmodels for autism suggest an abnormal construction of visual perceptualrepresentation or a deficit in executive functions. These modelspredict cerebral lesions in the temporo-occipital or frontal regions ofautistic patients. The present study aimed at studying the presence of symptoms of autism and visual agnosia in a 13 year old girl who had aright temporo-occipital cortical dysplasia that was surgically removedat the age of 7.
METHODS—Neuropsychological evaluation includedWechsler and Kaufman intelligence scales, a test of word fluency, digitspan, Corsi block, California verbal learning, Trail making, Bentonfacial recognition, Snoodgrass object recognition tests, Rivermead face learning subtest, and developmental test of visual perception. TheADI-R was used to show current and retrospective diagnosis of autisticdisorder. Neuroimagery included brain MRI, single photon emissioncomputed tomography (SPECT), and PET.
RESULTS—Brain MRI showed a right occipital defectand an abnormal hyperintensity of the right temporal cortex. PET andSPECT disclosed a left frontal hypometabolism together with the rightoccipital defect. Neuropsychological testing showed a visualapperceptive agnosia and executive function deficits. Psychiatric studyconfirmed the diagnosis of autistic disorder.
CONCLUSIONS—Although the possibilty that autismand visual agnosia were dissociable factors in this patient cannot beexcluded, the finding of both deficits supports the possibility thatoccipito-temporal lesions can predispose to the development of autism.

     

Clinical correlations of occipital epileptiform discharges in children.

OBJECTIVES: To determine the frequency of different causes of occipital epileptiform discharges (OEDs) in children and to analyze the EEG features that help predict epilepsy type and prognosis. METHODS: We identified children with OEDs in the absence of other focal discharges using an EEG database at our center; the presence of generalized spike-wave discharges (GSW) or slowing was not an exclusion criterion. Diagnosis, neurologic status, seizure semiology, and seizure remission status were recorded. RESULTS: Of 90 patients with OEDs, 50 (56%) had symptomatic seizures (18 with cerebral palsy, 11 with cerebral dysgenesis, 8 with genetic abnormalities); 31 (34%) had idiopathic seizures, including 6 with benign childhood epilepsy with occipital paroxysms (BCEOP), 8 (9%) had no seizures; and 1 (1%) had febrile seizures. Only two reported ictal visual symptoms. Eighty-seven percent with background slowing had symptomatic seizures, and 87% with normal backgrounds had idiopathic seizures (p < 0.001). Of 72 children with seizures and adequate follow-up, 28 of 45 (62%) with a normal background experienced seizure remission compared with 10 of 27 (37%) with background slowing (p = 0.04). Twenty of 81 patients with epilepsy had GSW. Twelve (60%) of the 20 GSW-positive patients had idiopathic epilepsy compared with 19 of 61 (31%) without GSW (p = 0.02). CONCLUSIONS: Most epilepsy in referred children with OEDs is symptomatic; syndromes such as BCEOP are rare. Visual ictal symptoms are rare. The presence of GSW or a normal background rhythm correlates with idiopathic seizures and a better prognosis.     

Autism and autistic behavior in Joubert syndrome.

To determine whether individuals with Joubert syndrome exhibit features of autism as defined by the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV), we examined 11 children with Joubert syndrome using the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule-Generic. Three children met DSM-IV criteria for autistic disorder and one for pervasive developmental disorder not otherwise specified. The other seven all demonstrated at least one DSM-IV symptom of autism, but did not meet criteria for a pervasive developmental disorder. Both total number of DSM-IV symptoms and number of social symptoms distinguished the autism and nonautism subgroups. In contrast, the two subgroups displayed similar levels of communication impairments and repetitive or stereotyped behavior. The key to diagnosing autism in Joubert syndrome is to focus on social behaviors, particularly milestones typically achieved very early in life (eg, attending to human voices, showing objects of interest, enjoyment of social interactions). Implications for the role of the cerebellum in nonmotor behavior and for clinical management of Joubert syndrome also are discussed.     

Visual and automatic investigation of epileptiform spikes in intracranial EEG recordings

PURPOSE: Performance of automatic spike-detection algorithms and interrater reliability of human EEG reviewers were investigated previously by using scalp EEG recordings. However, it is not known, whether the findings of these studies hold for intracranial recordings. To address this question, we analyzed spike detection in intracranial recordings by two human reviewers and three automatic systems covering major lines in the development of automatic spike-detection systems. METHODS: Intracranial recordings from subdural and intrahippocampal depth electrode contacts in seven patients were analyzed by two reviewers and three spike-detection systems: (a) The rule-based system by Gotman, (b) a two-stage system consisting of a linear predictor and a second rule-based stage, and (c) a system using wavelet coefficients of the intracranial EEG data. RESULTS: Agreement between the two human reviewers with respect to spike identification was <50%. The automatic systems achieved agreements of 24% (Gotman), 26% (wavelet detector), and 32% (two-stage system) with the individual human reviewers. In spite of the small proportion of agreements, the same anatomic regions were identified by human and automatic EEG analysis as generators for the majority of spikes. CONCLUSIONS: The poor agreement between the human EEG reviewers suggests that the definition of spikes and spike-like episodes in intracranial electrodes is far from unequivocal. Nevertheless, localizing information is highly consistent by either visual or automatic spike detection, independent of the algorithm used for automatic spike detection.     

Assessment of a computer program to detect epileptiform spikes.

This study compares an automated spike detection program to a group of 6 electroencephalographers. Since group members varied in experience, an expertise factor was devised to weight their scoring. EEGers underscored epileptiform events on 6 records in a manner analogous to the computer's storage of EEG segments. A summation of expertise factors was determined for every event. This sum was normalized and interpreted as a probability the event would be called a spike by a given EEGer. The performance of each scorer and of the computer at different amplitude thresholds was analyzed based on this probability. Higher rated scorers identified more subtle events. Lowering the threshold of the computer program produced a comparable increase in sensitivity. The increase in total events detected by the computer was linear over the range studied. While the proportion of false positive detections increased with lowering threshold, our readers have not found a moderate number of these distracting. We conclude that the computer system, while not as specific as an EEGer, can be as sensitive and can be a reliable screening editor for large amounts of monitoring data. On balance it is more effective than an EEGer for this limited purpose.     

Overlap of autistic and schizotypal traits in adolescents with Autism Spectrum Disorders

This study addresses the unraveling of the relationship between autism spectrum and schizophrenia spectrum traits in a population of adolescents with Autism Spectrum Disorders (ASD). Recent studies comparing isolated symptoms of both spectrum disorders as well as diagnostic criteria for each (DSM-IV-TR) suggest resemblances in the clinical phenotype. A group of 27 adolescents with ASD (11 to 18 years) and 30 typically developing adolescents, matched for age and gender, participated in this study. Within the ASD group 11 adolescents satisfied DSM-IV-TR criteria for schizotypal personality disorders. Autistic and schizotypal traits were identified by means of well validated questionnaires (Autism Questionnaire, AQ and Schizotypal Personality Questionnaire-Revised, SPQ). Significantly more schizotypal traits in adolescents with ASD were found than in typically developing controls. Besides high levels of negative symptoms, adolescents with ASD also displayed high levels of positive and disorganized symptoms. There appeared to be a relationship between the mean level of autistic symptoms and schizotypal traits, as well as specific associations between autistic symptoms and negative, disorganized and positive schizotypal symptoms within individuals. Schizotypal symptomatology in all sub dimensions that are reflected by the SPQ scores, was most prominently associated with attention switching problems of the autism symptoms from the AQ. These findings indicate that patients diagnosed with an ASD show schizophrenia spectrum traits in adolescence. Although other studies have provided empirical support for this overlap in diagnostic criteria between both spectrum disorders, the present findings add to the literature that behavioral overlap is not limited to negative schizotypal symptoms, but extends to disorganized and positive symptoms as well.     

Validity and reliability of the Childhood Autism Rating Scale with autistic adolescents

The validity and reliability of the Childhood Autism Rating Scale (CARS) for autistic adolescents was tested. In the first study, CARS scores for autistic children and adolescents (matched on nonverbal IQ, sex, and ethnicity) were compared. In the second study, a group of nonautistic, handicapped adolescents were administered the CARS and these scores were compared with those of a group of autistic adolescents (matched on age, nonverbal IQ, sex, and ethnicity). The CARS clearly discriminated the two adolescent groups, suggesting that the scale may be an adequate measure of autism in adolescence. Although the CARS total score did not discriminate the younger from older autistic subjects, some interesting age-related differences emerged for specific items. A recommendation is made for elimination of one of the items on the CARS that negatively correlates with the CARS total score for both autistic groups.This paper is based on a thesis submitted by the second author to North Texas State University in partial fulfillment of the requirements for the degree of Master of Arts. Portions of this research were presented at the Southwestern Psychological Association Annual Meeting in Ft. Worth, Texas, April 1986. The authors thank the children and their teachers who participated in this research. We are particularly grateful to Dallas Independent School District Special Education Director Dr. Ruth Turner, Ms. Alberta Rogers, Administrative Assistant, and the Dallas Autism Program staff who helped in both training raters and coordinating this project.     

Clinical correlations of electroencephalographic occipital epileptiform paroxysms in children.

A longitudinal prospective approach was used to investigate clinical correlations of interictal occipital paroxysms with or without fixation-off sensitivity (FOS). Occipital paroxysms were recorded in the electroencephalograms (EEGs) of 76 children with heterogeneous clinical conditions including seizures in 39 patients. Occipital paroxysms with FOS (42 patients ) were only fractionally more frequent than non-FOS (34 patients ) and were not specific of any clinical condition. Although present and FOS-related in all 11 children with benign childhood epilepsies with occipital paroxysms (CEOP), they were also frequently encountered in symptomatic occipital epilepsy. The differentiation of CEOP from other syndromes established on clinical grounds could also be aided by the analysis of background EEG activity that was frequently significantly more abnormal in symptomatic than CEOP. Clinical characteristics and ictal seizure semiology as well as follow-up clearly distinguish two type of idiopathic CEOP syndromes: (1) early onset type or Panayiotopoulos syndrome characterized by excellent prognosis and rare, prolonged nocturnal seizures with tonic deviations of the eyes and vomiting, and (2) late onset or Gastaut type showing a common ictal visual symptomatology, co-occurrence of migraine, diurnal complex partial seizures and less favourable EEG-clinical prognosis.     

Cognitive and behavioral effects of nocturnal epileptiform discharges in children with benign childhood epilepsy with centrotemporal spikes

This review addresses the effects of subclinical localized epileptiform discharges during sleep in children with benign childhood epilepsy with centrotemporal spikes (BCECTS) on cognition and behavior. A diversity of educational deficits, behavioral impairments, language delay, and neuropsychological test results have been reported in children with BCECTS. The occurrence of atypical seizure characteristics seems to be related to language delay, and several atypical EEG characteristics are related to cognitive or behavioral problems. It remains to be shown whether treatment of nocturnal discharges in children with BCECTS is indicated to improve cognitive and behavioral problems.